Phase II Study of the Use of Neoadjuvant Cabazitaxel With Hormonal Treatment in Patients Operable Prostate Cancer, Assess the Efficacy and Toxicity of Cabazitaxel, and Explore Potential Predictive and Prognostic Markers of Clinical Outcome

NCT ID: NCT04622761

Last Updated: 2021-01-05

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-15
• Study Completion Date: 2026-05-02

Brief Summary

This study is evaluating the efficacy of cabazitaxel and hormonal treatment as neoadjuvant treatment for patients with clinically operable disease suitable for surgery, and a high risk of relapse after surgery

Detailed Description

This study is evaluating the efficacy of cabazitaxel and hormonal treatment (LHRH analogues) as neoadjuvant treatment for patients with clinically operable disease suitable for surgery (no lymph node, visceral or bony metastases), and a high risk of relapse after surgery (5 year risk of relapse).

Patients will receive four cycles of neoadjuvant treatment (cabazitaxel treatment and 3 months LHRH treatment) unless there is evidence of disease progression, unacceptable toxicity or patient request to withdraw consent.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

control

Immediate surgery (radical prostatectomy) (standard care)

Group Type: NO_INTERVENTION

No interventions assigned to this group

treatment

14 days prior to starting Cabazitaxel patients will take 50mg Bicalutamide once daily for 21 days.

7 days prior to starting Cabazitaxel patients will be given 3 months LHRH treatment via injection. The entire dose will be administered via one injection 7 days prior to starting Cabazitaxel. This may be either leuprorelin or goserelin acetate and should be given as per local practice.

At least 30 minutes prior to each administration of Cabazitaxel, patients will be administered IV premedication consisting of:

50mg Ranitidine 10mg Chlorphenamine 8mg Dexamethasone Daily from Day 1 until end of Cabazitaxel treatment patients will take 10mg Prednisolone once daily from Day 1 until end of Cabazitaxel treatment Day 1 of each cycle - Patients will receive Cabazitaxel 25 mg/m2 intravenously over one hour every 21 days (on Day 1 of each cycle). Treatment will be continued for 4 cycles.

Group Type: EXPERIMENTAL

Cabazitaxel

Intervention Type: DRUG

Patients will receive Cabazitaxel 25 mg/m2 * intravenously over one hour every 21 days (on Day 1 of each cycle). Treatment will be continued for 4 cycles unless disease progression, unacceptable toxicity or patient request. These patients will have surgery (radical prostatectomy) 4-86 weeks following treatment.

*Cabazitaxel dose should be capped at 50mg (BSA=2)

Interventions

Cabazitaxel

Patients will receive Cabazitaxel 25 mg/m2 * intravenously over one hour every 21 days (on Day 1 of each cycle). Treatment will be continued for 4 cycles unless disease progression, unacceptable toxicity or patient request. These patients will have surgery (radical prostatectomy) 4-86 weeks following treatment.

*Cabazitaxel dose should be capped at 50mg (BSA=2)

Intervention Type: DRUG

Other Intervention Names

jevtana, XRP6258, RPR116258A

Eligibility Criteria

Inclusion Criteria

1. Aged ≥18 years

2. ECOG performance status 0-1 (Appendix 2)

3. Diagnosis of high risk prostate cancer as defined by one or more of the following: clinically T2c/T3, Gleason 8-10 and or PSA >10ng/ml

4. Appropriate candidate for radical prostatectomy

5. Life expectancy greater than 10 years

6. Adequate organ function as evidenced by peripheral blood counts and serum chemistries at enrolment

7. Ability and capacity to consent and comply with study and follow-up procedures

8. Fit to receive chemotherapy

Exclusion Criteria

1. Locally advanced or metastatic disease

2. Patients with a history of other previous malignancy except treated CIN or non melanomatous skin cancer

3. Grade ≥2 peripheral neuropathy

4. Grade ≥2 stomatitis

5. History of severe hypersensitivity reaction (≥ grade 3) to taxane

6. History of severe hypersensitivity reaction (≥ grade 3) to polysorbate 80 containing drugs

7. Other concurrent serious illness or medical conditions

8. Inadequate organ and bone marrow function as evidenced by:

1. Haemoglobin <10.0 g/dL

2. Absolute neutrophil count <1.5 x 109/L

3. Platelet count <100 x 109/L

4. AST/SGOT and/or ALT/SGPT >1.5 xULN

5. Total bilirubin >1.5 x ULN

6. Serum creatinine >1.5 x ULN (if creatinine is 1.0 - 1.5 xULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance <60mL/min should be excluded - see Appendix 3)

9. Uncontrolled diabetes mellitus

10. Active uncontrolled gastro oesophageal reflux disease (GORD)

11. Active infection requiring systemic antibiotic or antifungal medication

12. Participation in another clinical trial with any investigational drug within 30 days prior to study enrolment

13. Concurrent or planned treatment with strong inhibitors of cytochrome P450 3A4/5 (a 1-week washout period is necessary for patients who are already on these treatments - see Appendix 5 for a list of CYP3A inhibitors)

14. Concurrent or planned treatment with strong inducers of cytochrome P450 3A4/5 (a 1-week washout period is necessary for patients who are already on these treatments) - see Appendix 4 for a list of CYP3A inducers)

15. Contraindications or sensitivity to GCSF treatments

16. History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias of Grade > 2 (NCI CTCAE, version 4.03), thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (e.g., pericardial effusion restrictive cardiomyopathy) within 6 months prior to first dose of study drug. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.

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• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Liverpool

OTHER

Sponsor Role: collaborator

The Clatterbridge Cancer Centre NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Marie Maguire

Role: CONTACT

maria.maguire2@nhs.net

0151 556 5321

Claire Taylor

Role: CONTACT

chrome@liverpool.ac.uk

0151 795 14010

Other Identifiers

RDD630

Identifier Type: -

Identifier Source: org_study_id